Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000941965
Ethics application status
Approved
Date submitted
28/07/2020
Date registered
21/09/2020
Date last updated
16/06/2021
Date data sharing statement initially provided
21/09/2020
Date results information initially provided
16/06/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
The effect of cannabidiol (CBD) on exercise physiology and bioenergetics
Scientific title
A randomised, double-blind, placebo-controlled crossover phase IIa pilot trial exploring the effect of purified oral cannabidiol (CBD) on exercise physiology and bioenergetics in healthy, endurance-trained individuals
Secondary ID [1] 301383 0
CT-2020-CTN-02454-1
Universal Trial Number (UTN)
U1111-1256-2200
Trial acronym
CANRUN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metabolic Disorders 317640 0
Condition category
Condition code
Metabolic and Endocrine 315721 315721 0 0
Metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Oral Cannabidiol in Medium Chain Triglyceride Oil (Schedule 4 Drug); 300 mg (single dose)

All trials will be separated by a washout period of at least 7 days.

As this is an ‘acute dosing’ trial (i.e. using a single dose of CBD per research session); compliance does not need to be monitored.
Intervention code [1] 317688 0
Treatment: Drugs
Comparator / control treatment
Placebo; Medium Chain Triglyceride Oil
Control group
Placebo

Outcomes
Primary outcome [1] 323930 0
Oxygen utilisation (VO2) during submaximal intensity exercise (~75%HRmax) while the subject is on a treadmill using a metabolic cart
Timepoint [1] 323930 0
90-150 min post-drug administration
Secondary outcome [1] 383367 0
Time to fatigue during an incremental exercise test (approaching maximal intensity) while subject is on a treadmill as measured with a stopwatch
Timepoint [1] 383367 0
180-200 min post-drug administration
Secondary outcome [2] 384336 0
Heart rate as measured with an upper arm blood pressure monitor (baseline, 75-, 150 and 260 min post-drug administration) while the subject is at rest and an exercising chest strap heart monitor (110-, 130-, 150- and 180-200 min post-drug administration) while the subject is exercising on a treadmill
Timepoint [2] 384336 0
Baseline, ~75- 110-, 130-, 150-, ~180-200 and 260 min post-drug administration
Secondary outcome [3] 384337 0
Aerobic capacity (VO2max) while subject is on a treadmill using a metabolic cart.
Timepoint [3] 384337 0
~200 min post-drug administration.
Secondary outcome [4] 384338 0
Blood glucose concentrations while subject is on a treadmill using a blood glucose monitor
Timepoint [4] 384338 0
 110-, 130-, 150- and ~200 min post-drug administration.
Secondary outcome [5] 384339 0
Plasma concentrations of IL-6.
Timepoint [5] 384339 0
Baseline, 150-, 200-and 260 min post-drug administration.
Secondary outcome [6] 384340 0
Plasma concentrations of Mb
Timepoint [6] 384340 0
Baseline, 150-, 200-and 260 min post-drug administration.
Secondary outcome [7] 384341 0
Plasma concentrations of LPS
Timepoint [7] 384341 0
Baseline, 150-, 200-and 260 min post-drug administration.
Secondary outcome [8] 384342 0
Score on the Profile of Mood States (POMS)
Timepoint [8] 384342 0
Baseline, 75-, 150 ~200 and 260 min post-drug administration.
Secondary outcome [9] 384343 0
Score on the Spielberger 6-item State-Trait Anxiety Inventory (STAI-Y)
Timepoint [9] 384343 0
Baseline, 75-, 150-, ~200 and 260-min post-drug administration.
Secondary outcome [10] 384344 0
Rating of perceived exertion (RPE) on the Borg scale
Timepoint [10] 384344 0
110-, 130-, 150- and ~180-200 post-drug administration.
Secondary outcome [11] 384345 0
Affective valence (pleasure–displeasure) on the Feelings Scale (FS)
Timepoint [11] 384345 0
110-, 130-, 150- and ~180-200 post-drug administration.
Secondary outcome [12] 384346 0
Subjective ratings of gastrointestinal (GI ) comfort on GI Comfort Visual Analog Scales (VASs)
Timepoint [12] 384346 0
Baseline, 75-, 150-, ~200 and 260 min post-drug administration.
Secondary outcome [13] 384347 0
Subjective ratings of muscle soreness as assessed on a scale of 0–10, where 0 represents “not at all” and 10 represents “extremely”
Timepoint [13] 384347 0
On waking the morning following each experimental trial.
Secondary outcome [14] 384348 0
Plasma cannabinoid concentrations 
Timepoint [14] 384348 0
Baseline, 75-, 150-, ~200 and 260 min post-drug administration.
Secondary outcome [15] 386048 0
Blood lactate concentrations while the subject is on a treadmill using a blood glucose monitor
Timepoint [15] 386048 0
 110-, 130-, 150-, ~200 min post-drug administration.
Secondary outcome [16] 386049 0
Plasma concentrations of IL-1ß
Timepoint [16] 386049 0
Baseline, 150-, 200-and 260 min post-drug administration.
Secondary outcome [17] 386052 0
Plasma concentrations of CK
Timepoint [17] 386052 0
Baseline, 150- and ~200- and 260 min post-drug administration.
Secondary outcome [18] 386056 0
Plasma concentrations of Claudin-3
Timepoint [18] 386056 0
Baseline, 150-, 200-and 260 min post-drug administration.
Secondary outcome [19] 386057 0
Subjective ratings of sleep quality assessed on a scale of –5 to +5, where –5 represents “very poor”, 0 represent “fair” and +5 represents “very good”
Timepoint [19] 386057 0
On waking the morning following each experimental trial.
Secondary outcome [20] 386058 0
Plasma endocannabinoid concentrations
Timepoint [20] 386058 0
Baseline, 75-, 150-, ~200 and 260-min post-drug administration.
Secondary outcome [21] 387081 0
Plasma TNF-a concentrations
Timepoint [21] 387081 0
Baseline, 150-, 200-and 260 min post-drug administration.

Eligibility
Key inclusion criteria
a) greater than or equal to 18 and less than or equal to 45 years of age;
(b) Endurance-trained individuals; i.e. who have run an average of greater than or equal to 40 km·wk-1 for the last month (or more) and can sustain moderate intensity running exercise for >60-minutes;
(c) No reported use of cannabis or cannabinoids within the past 3 months; to be confirmed by a negative urine drug screen (UDS) at the medical screening; and
(d) Proficient in English (i.e. must not require an English translator).
Minimum age
18 Years
Maximum age
45 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
(a) Cannabis dependence or any other drug or alcohol dependence, as per the International Statistical Classification of Diseases 10th Revision (ICD)-10 criteria or at a medical doctor’s discretion; 
(b) A history (self-reported) of allergic reaction (e.g. rhinitis, urticaria, contact dermatitis, anaphylaxis) to cannabis, cannabis products or cannabinoids; 
(c) A history (self-reported) of a clinically significant adverse response to cannabidiol (CBD); 
(d) A history of a major psychiatric disorder within the previous 12 months, as per the Diagnostic and Statistical Manual of Mental Disorders (DSM)-V criteria or at the medical doctor’s discretion, except, mild to moderate depression (score <20 on the Beck Depression Inventory [BDI] or mild to moderate anxiety (score <16 on the Beck Anxiety Inventory [BAI];
(e) A history of attempted suicide or current suicide ideation as determined by a score >0 on Question 9 of the Patient Health Questionnaire (PHQ)-9; 
(f) A (self-reported) history of, or current, cardiovascular, respiratory, renal, neurological, gastrointestinal, or endocrinological disorders; 
(g) A major illness or injury that interrupted their usual training routine for a period of greater than or equal to 3 weeks during the past 3 months; 
(h) Inability to refrain from consuming alcohol (24 h) and caffeine (12 h) prior to each experimental trial; 
(i) Inability to refrain from using anti-inflammatory medications (24 h) prior to each experimental trial; 
(j) Inability to refrain from using other central nervous system active drugs (e.g. cannabis, opioids, benzodiazepines) while participating in this project; 
(k) Use of medications that may influence CBD metabolism (e.g. inducers or inhibitors of the CYP450 enzyme system);
(l) Use of medications handled by transporter proteins or CYP enzymes that are inhibited by CBD, such as anticoagulants, calcium channel blockers, beta blockers, sulfonylureas and anti-convulsants; and 
(m) Required to complete mandatory drug testing for cannabis (e.g. workplace testing, anti-doping in sport testing). 

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Numbered containers
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomisation using a random number generator
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Not applicable
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
As the investigation is a pilot trial, we expect it will be underpowered to achieve statistical significance at the 5% level. As such, we will use a descriptive approach in which confidence intervals (CIs) other than 95% are interpreted in relation to the minimum clinically important difference (MCID). The effect of CBD will be said to warrant further investigation if the upper limit of the 80% CI for the change in the primary outcome includes the proposed MCID of 5%, but not zero.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
31/08/2020
Date of last participant enrolment
Anticipated
1/01/2021
Actual
12/10/2020
Date of last data collection
Anticipated
1/02/2021
Actual
23/10/2020
Sample size
Target
10
Accrual to date
Final
10
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 305823 0
Charities/Societies/Foundations
Name [1] 305823 0
Lambert Initiative for Cannabinoid Therapeutics
Country [1] 305823 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
Camperdown, NSW, 2050
Country
Australia
Secondary sponsor category [1] 306267 0
None
Name [1] 306267 0
Address [1] 306267 0
Country [1] 306267 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306091 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 306091 0
Research Ethics and Governance Office (REGO)
Royal Prince Alfred Hospital
Missenden Road
Camperdown NSW 2050
Ethics committee country [1] 306091 0
Australia
Date submitted for ethics approval [1] 306091 0
24/02/2020
Approval date [1] 306091 0
24/03/2020
Ethics approval number [1] 306091 0
X20-0063

Summary
Brief summary
This study is a randomised, crossover, double-blinded, single-dose experimental trial investigating the effects of purified, oral cannabidiol (CBD) on exercise physiology and bioenergetics in healthy individuals. Participants will complete two experimental sessions involving either (1) CBD (300mg) or (2) Placebo (0mg). Trials will be conducted at the Charles Perkins Centre Research. We hypothesise CBD will decrease submaximal oxygen consumption during moderate intensity exercise (~75% HRmax).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 102670 0
Prof Paul Haber
Address 102670 0
University of Sydney
Level 6 South Wing,
King George Building,
Missenden Road, Camperdown
NSW, 2050
Country 102670 0
Australia
Phone 102670 0
+61 2 9515 6419
Fax 102670 0
Email 102670 0
[email protected]
Contact person for public queries
Name 102671 0
Ms Ayshe Sahinovic
Address 102671 0
Room 611
Brain and Mind Centre
94 Mallett St, Camperdown
NSW, 2050
Country 102671 0
Australia
Phone 102671 0
+61 449 786 042
Fax 102671 0
Email 102671 0
[email protected]
Contact person for scientific queries
Name 102672 0
Dr Danielle McCartney
Address 102672 0
Room 611
Brain and Mind Centre
94 Mallett St, Camperdown
NSW, 2050
Country 102672 0
Australia
Phone 102672 0
+61 404 656 000
Fax 102672 0
Email 102672 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All of the individual participant data collected during the trial, after de-identification
When will data be available (start and end dates)?
Immediately following publication (via request), no end date
Available to whom?
Only researchers who provide methodologically sound proposal
Available for what types of analyses?
Only to achieve the aims of the approved proposal
How or where can data be obtained?
By contacting the principal investigator, Professor Paul Haber, via email at [email protected]


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseEffects of Cannabidiol on Exercise Physiology and Bioenergetics: A Randomised Controlled Pilot Trial.2022https://dx.doi.org/10.1186/s40798-022-00417-y
N.B. These documents automatically identified may not have been verified by the study sponsor.